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Cesium carbonate → 4-(5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-2-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1923138
ノート
印刷プレビュー

反応式

HRID 1923138 の反応式
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][S:19](=[O:23])(=[O:22])[CH2:18][CH2:17]4)[CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH2:30]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:30]([C:32]1[N:33]([C:2]2[N:3]=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:13][CH:14]([N:16]5[CH2:17][CH2:18][S:19](=[O:22])(=[O:23])[CH2:20][CH2:21]5)[CH2:15]4)[S:8][C:6]=3[N:7]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596058185-Chloro-2-[3-(1,1-Dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine

生成物 1

HCID 596058284-(5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-2-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine
収率 60.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
145 °C

実験手順

A mixture of 5-chloro-2-[3-(1,1-Dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine (150 mg, 0.33 mmol), 2-ethylbenzimidazole (58 mg, 0.39 mmol), tris(dibenzylideneacetone)dipalladium (15 mg, 0.02 mmol), Xphos (31 mg, 0.07 mmol) and Cs2CO3 (213 mg, 0.65 mmol) in dioxane (3 mL) was purged with argon then heated at 145° C. for 45 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) affording 436 as a foam (113 mg, 60%). LCMS (Method I): RT 2.59 min, [M+H]+ 569.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.79-7.75 (m, 1 H); 7.33-7.27 (m, 2 H); 4.41 (m, 4 H); 4.02 (s, 2 H); 3.91-3.81 (m, 4 H); 3.72 (m, 2 H); 3.39-3.30 (m, 3 H); 3.16 (m, 2 H); 3.08 (m, 4 H); 2.90-2.85 (m, 4 H) and 1.44 (t, J=7.5 Hz, 3 H)

後処理

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)

出典と根拠

ORDレコード
ord-8a822e7dd38e4a088c654fb975c79548
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08173650B2

反応ノート

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